rs11599284

chr10-133230505-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003577.3(UTF1):c.217G>A(p.Gly73Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,444,072 control chromosomes in the GnomAD database, including 12,385 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.099 (983 hom., cov: 32)
  • Exomes 𝑓: 0.13 (11402 hom.)
• Consequence: UTF1 NM_003577.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

Genes affected

UTF1 (HGNC:12634): (undifferentiated embryonic cell transcription factor 1) The protein encoded by this gene is a leucine zipper-containing transcriptional coactivator that may link the upstream activator ATF2 with the basal transcription complex. The encoded protein is closely associated with chromatin and is required for the proper differentiation of embryonic carcinoma and embryonic stem cells. Found nearly exclusively in pluripotent cells, this protein can also serve as a transcriptional repressor. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017513335).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UTF1	NM_003577.3	c.217G>A	p.Gly73Arg	missense_variant	1/2	ENST00000304477.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UTF1	ENST00000304477.3	c.217G>A	p.Gly73Arg	missense_variant	1/2	1	NM_003577.3	P1

Frequencies

GnomAD3 genomes AF: 0.0990 AC: 14969 AN: 151258 Hom.: 982 Cov.: 32

Gnomad AFR AF: 0.0259

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.0878

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.157

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.107

GnomAD3 exomes AF: 0.151 AC: 10919 AN: 72356 Hom.: 922 AF XY: 0.154 AC XY: 6459 AN XY: 41856

Gnomad AFR exome AF: 0.0211

Gnomad AMR exome AF: 0.197

Gnomad ASJ exome AF: 0.0949

Gnomad EAS exome AF: 0.101

Gnomad SAS exome AF: 0.204

Gnomad FIN exome AF: 0.140

Gnomad NFE exome AF: 0.120

Gnomad OTH exome AF: 0.118

GnomAD4 exome AF: 0.128 AC: 165385 AN: 1292706 Hom.: 11402 Cov.: 37 AF XY: 0.130 AC XY: 83071 AN XY: 637704

Gnomad4 AFR exome AF: 0.0231

Gnomad4 AMR exome AF: 0.186

Gnomad4 ASJ exome AF: 0.0963

Gnomad4 EAS exome AF: 0.122

Gnomad4 SAS exome AF: 0.200

Gnomad4 FIN exome AF: 0.134

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.121

GnomAD4 genome AF: 0.0989 AC: 14964 AN: 151366 Hom.: 983 Cov.: 32 AF XY: 0.101 AC XY: 7504 AN XY: 73970

Gnomad4 AFR AF: 0.0258

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.0878

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.105

Alfa AF: 0.111 Hom.: 241

Bravo AF: 0.0933

TwinsUK AF: 0.119 AC: 442

ALSPAC AF: 0.117 AC: 450

ExAC AF: 0.0958 AC: 2091

Asia WGS AF: 0.139 AC: 465 AN: 3350

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.44
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.51	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	0.99	P
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.048
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.023	D
Polyphen		0.53	P
Vest4		0.043
MutPred		0.16		Gain of MoRF binding (P = 0.0054);
MPC		1.8
ClinPred		0.016	T
GERP RS		2.0
Varity_R		0.23
gMVP		0.024

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11599284; hg19: chr10-135044009; COSMIC: COSV58678281; COSMIC: COSV58678281;